Fungal Stress Responses.

Trehalose Biosynthesis.

One of the current goals of the Washington laboratory is to determine the structure and function of proteins involved in trehalose biosynthesis. We are particularly interested in how this pathway contributes to fungal pathogenesis and how we can exploit it as an antifungal drug target. 

Trehalose is a disaccharide composed of two molecules of glucose that is required for pathogenic fungi to survive in their human hosts. Trehalose biosynthesis is a two-step process. Trehalose-6-phosphate synthase (Tps1) converts UDP-glucose (UDP-Glc) and glucose-6-phosphate (G6P) to trehalose-6-phosphate (T6P). Subsequently, trehalose-6-phosphate phosphatase (Tps2) converts T6P to trehalose. Additionally, C. albicans and A. fumigatus express Tps3, a protein predicted to lack catalytic activity and mediate protein-protein interactions. The trehalose biosynthesis pathway is conserved among all major fungal pathogens and yet is absent in mammals.

Trehalose plays a major role as a stress molecule in fungal pathogens. Trehalose biosynthesis is induced by heat stress. We are particularly interested in how trehalose is induced by heat stress and how trehalose contributes to fungal thermotolerance.